Long-Term Effects of Axotomy on Excitability and Growth of Isolated Aplysia
Sensory Neurons in Cell Culture: Role of cAMP.
Supinder S. Bedi, Ali Salim, Shanping Chen, and David L. Glanzman.
Department of Physiological Science, UCLA, 2859 Slichter Hall, Box 951568,
Los Angeles, CA 90095-1568. Brain Research Institute, UCLA, Los Angeles, CA
90095.APStracts 4:320N, 1997.
ABSTRACT
Crushing nerves in Aplysia which contain the axons of central sensory neurons
causes the neurons to become hyperexcitable and to sprout new processes.
Previous experiments which examined the effects of axonal injury on Aplysia
sensory neurons have been performed in the intact animal or in the semi-intact
central nervous system of Aplysia. It has therefore been unclear to what
extent the long-term neuronal consequences of injury are due to intrinsic or
extrinsic cellular signals. To determine whether injury-induced changes in
Aplysia sensory neurons are due to intrinsic or extrinsic signals, we have
developed an in vitro model of axonal injury. Isolated central sensory neurons
grown for 2 days in cell culture were axotomized. Approximately 24 hr after
axotomy sensory neurons exhibited a greater excitabilityÄreflected, in part,
as a significant reduction in spike accommodationÄand greater neuritic
outgrowth than did control (unaxotomized) neurons. Rp-cAMPS, an inhibitor of
protein kinase A, blocked both the reduction in accommodation and increased
neuritic outgrowth induced by axotomy. Rp- cAMPS also blocked similar, albeit
smaller, alterations observed in control sensory neurons over the 24-hr period
of our experiments. These results indicate that axonal injury elevates cAMP
levels within Aplysia sensory neurons, and that this elevation is directly
responsible, in part, for the previously described long-term
electrophysiological and morphological changes induced in Aplysia sensory
neurons by nerve crush. In addition, the results indicate that control sensory
neurons in culture are also undergoing injury-related electrophysiological and
structural changes, probably due to cellular processes triggered when the
neurons are axotomized during cell culturing. Finally, the results provide
support for the idea that the cellular processes activated within Aplysia
sensory neurons by injury, and those activated during long-term behavioral
sensitization, overlap significantly.

Received 19 November 1996; accepted in final form 11 November 1997.
APS Manuscript Number J918-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 December 1997